Over the past several years our research on determination of the retina and lens has led us to a revised and refined view of how these tissues are formed during development. During the period of proposed support our first goal will be to fill in key gaps that still remain in our understanding of the inductive interactions controlling the formation of these tissues. Much of the proposed work will utilize examination of Xenopus embryos, which provide an excellent system for manipulating tissues during early development. In addition we will undertake studies of mouse embryonic lens determination because of the availability of genetic information that will be of great help in understanding how this process is controlled. Foremost among our studies will be examination of tissue interactions responsible for the phenotype (blocked retina and lens formation) of Small-eye mice, now known to be deficient in the homeobox gene Pax-6. Because this is the same gene responsible for the human syndrome Aniridia, it is expected that our work will be of significant value in understanding the origin of this clinical problem. The second phase of our work will focus on the signal transduction mechanisms responsible for retina and lens formation. With information in hand about tissue interactions, we can define the likely source of signals and propose to attempt to identify them. In addition we will plan to investigate what receptors and second messenger systems control retina and lens determination, primarily by using a number of existing dominant negative constructs for key signal transduction elements.